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1.
BMC Cancer ; 24(1): 578, 2024 May 11.
Article En | MEDLINE | ID: mdl-38734620

OBJECTIVE: This study aims to develop a nomogram integrating inflammation (NLR), Prognostic Nutritional Index (PNI), and EBV DNA (tumor burden) to achieve personalized treatment and prediction for stage IVA NPC. Furthermore, it endeavors to pinpoint specific subgroups that may derive significant benefits from S-1 adjuvant chemotherapy. METHODS: A total of 834 patients diagnosed with stage IVA NPC were enrolled in this study and randomly allocated into training and validation cohorts. Multivariate Cox analyses were conducted to identify independent prognostic factors for constructing the nomogram. The predictive and clinical utility of the nomogram was assessed through measures including the AUC, calibration curve, DCA, and C-indexes. IPTW was employed to balance baseline characteristics across the population. Kaplan-Meier analysis and log-rank tests were utilized to evaluate the prognostic value. RESULTS: In our study, we examined the clinical features of 557 individuals from the training cohort and 277 from the validation cohort. The median follow-up period was 50.1 and 49.7 months, respectively. For the overall cohort, the median follow-up duration was 53.8 months. The training and validation sets showed 3-year OS rates of 87.7% and 82.5%, respectively. Meanwhile, the 3-year DMFS rates were 95.9% and 84.3%, respectively. We created a nomogram that combined PNI, NRI, and EBV DNA, resulting in high prediction accuracy. Risk stratification demonstrated substantial variations in DMFS and OS between the high and low risk groups. Patients in the high-risk group benefited significantly from the IC + CCRT + S-1 treatment. In contrast, IC + CCRT demonstrated non-inferior 3-year DMFS and OS compared to IC + CCRT + S-1 in the low-risk population, indicating the possibility of reducing treatment intensity. CONCLUSIONS: In conclusion, our nomogram integrating NLR, PNI, and EBV DNA offers precise prognostication for stage IVA NPC. S-1 adjuvant chemotherapy provides notable benefits for high-risk patients, while treatment intensity reduction may be feasible for low-risk individuals.


Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Neoplasm Staging , Nomograms , Humans , Male , Female , Middle Aged , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/mortality , Nasopharyngeal Carcinoma/pathology , Chemotherapy, Adjuvant/methods , Prognosis , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/pathology , Inflammation , Adult , Nutrition Assessment , Herpesvirus 4, Human/isolation & purification , Tegafur/therapeutic use , Tegafur/administration & dosage , DNA, Viral , Drug Combinations , Oxonic Acid/therapeutic use , Oxonic Acid/administration & dosage , Aged , Kaplan-Meier Estimate
2.
Zhonghua Nei Ke Za Zhi ; 63(5): 490-494, 2024 May 01.
Article Zh | MEDLINE | ID: mdl-38715487

The study presents an analysis of the diagnostic and treatment protocol for a patient with a first episode of nasopharyngeal carcinoma who also has Sjogren's syndrome and Epstein-Barr Virus (EBV) positive cerebrospinal fluid, as detected through metagenomic next-generation sequencing (mNGS). It reviews existing literature to examine the connections between EBV and various conditions including Sjogren's syndrome, encephalitis or meningitis, and nasopharyngeal carcinoma, emphasizing the importance of EBV positive cerebrospinal fluid. The study focuses on a case from the Eighth Medical Center of the General Hospital of the People's Liberation Army, where a patient was admitted with headaches as the primary symptom on March 3, 2021. This patient had a history of Sjogren's syndrome and was later diagnosed with nasopharyngeal carcinoma. The research involved reviewing both domestic and international databases for cases related to cerebrospinal fluid EBV positive encephalitis or meningitis, and nasopharyngeal carcinoma. It aimed to aggregate data on demographics, initial symptoms, treatment methods, and patient outcomes. Findings suggest that positive cerebrospinal fluid EBV is linked to autoimmune diseases, viral encephalitis or meningitis, and nasopharyngeal carcinoma, albeit infrequently in the context of Sjogren's syndrome. Notably, EBV positive cerebrospinal fluid is commonly associated with recurrent nasopharyngeal carcinoma rather than initial episodes. The study concludes that for patients with an immune condition, exhibiting symptoms like headaches or cranial nerve issues, or in cases where nasopharyngeal carcinoma is suspected, early testing through cerebrospinal fluid mNGS or EBV DNA is recommended. This approach facilitates risk assessment, prognosis determination, and the creation of individualized treatment plans.


Herpesvirus 4, Human , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Sjogren's Syndrome , Humans , Sjogren's Syndrome/cerebrospinal fluid , Sjogren's Syndrome/diagnosis , Sjogren's Syndrome/complications , Sjogren's Syndrome/virology , Nasopharyngeal Carcinoma/virology , Nasopharyngeal Carcinoma/diagnosis , Nasopharyngeal Carcinoma/cerebrospinal fluid , Herpesvirus 4, Human/isolation & purification , Nasopharyngeal Neoplasms/virology , Nasopharyngeal Neoplasms/diagnosis , Nasopharyngeal Neoplasms/cerebrospinal fluid , Epstein-Barr Virus Infections/cerebrospinal fluid , Epstein-Barr Virus Infections/diagnosis , Epstein-Barr Virus Infections/complications , High-Throughput Nucleotide Sequencing
3.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(2): 319-330, 2024 Feb 28.
Article En, Zh | MEDLINE | ID: mdl-38755729

Hepatic lymphoepithelioma-like carcinoma (LELC) is an extremely rare malignant tumor characterized by undifferentiated malignant epithelial cells and significant lymphatic infiltration. Hepatic LELC mainly includes lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) and lymphoepithelioma-like intrahepatic cholangiocarcinoma (LEL-CC). Epstein-Barr virus (EBV) infection is considered as an important factor in LELC carcinogenesis. Since 2005, Xiangya Hospital of Central South University has treated a total of 3 patients with EBV-associated LEL-CC, which all showed liver masses by CT scans. After surgical resection, the EBV encoded RNA (EBER) and CK19 expression in all 3 patients were positive, and pathological examination confirmed EBV-associated LEL-CC. Two patients had a good postoperative prognosis, while 1 patient received relevant immunotherapy and chemotherapy after surgery. Based on the analysis of existing literature, the author believes that hepatic LELC can be included in the classification of liver tumors, which will provide new ideas for the accurate diagnosis and treatment of hepatic LELC.


Bile Duct Neoplasms , Cholangiocarcinoma , Epstein-Barr Virus Infections , Humans , Cholangiocarcinoma/pathology , Cholangiocarcinoma/virology , Male , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/virology , Epstein-Barr Virus Infections/complications , Middle Aged , Herpesvirus 4, Human/genetics , Herpesvirus 4, Human/isolation & purification , Bile Ducts, Intrahepatic/pathology , Female , Liver Neoplasms/virology , Liver Neoplasms/pathology
4.
New Microbiol ; 47(1): 52-59, 2024 May.
Article En | MEDLINE | ID: mdl-38700884

Monitoring Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection after transplantation is recommended to enable preemptive therapy. However, the most suitable sample type remains unclear. Patients who underwent hematopoietic stem cell or liver transplantation were included in this study. Viral loads in sequential whole-blood and plasma samples were retrospectively analyzed. EBV DNA was detected more frequently in whole blood (55%) than in plasma (18%). The detection rate of CMV DNA was similar between the two sample types. The correlation of viral loads between the two sample types were 0.515 and 0.688 for EBV and CMV, respectively. Among paired samples in which EBV DNA was detected in whole blood, the plasma EBV detection rate was significantly higher in patients who underwent hematopoietic stem cell transplantation than in those who underwent liver transplantation. The viral DNA load in whole blood and plasma showed similar trends. The EBV detection rate was higher in whole blood, and a high correlation was observed between CMV DNA loads and whole blood and plasma. These results indicate that whole blood is more sensitive for monitoring both EBV and CMV, whereas plasma is a potential alternative sample for monitoring CMV.


Cytomegalovirus Infections , Cytomegalovirus , Epstein-Barr Virus Infections , Herpesvirus 4, Human , Viral Load , Humans , Cytomegalovirus/genetics , Cytomegalovirus/isolation & purification , Cytomegalovirus Infections/virology , Cytomegalovirus Infections/blood , Cytomegalovirus Infections/diagnosis , Herpesvirus 4, Human/genetics , Herpesvirus 4, Human/isolation & purification , Epstein-Barr Virus Infections/virology , Epstein-Barr Virus Infections/blood , Epstein-Barr Virus Infections/diagnosis , Male , Female , Middle Aged , Adult , Retrospective Studies , DNA, Viral/blood , Young Adult , Hematopoietic Stem Cell Transplantation , Aged , Plasma/virology , Liver Transplantation , Adolescent
5.
In Vivo ; 38(3): 1477-1482, 2024.
Article En | MEDLINE | ID: mdl-38688594

BACKGROUND/AIM: Fibrin-associated diffuse large B-cell lymphoma (FA-DLBCL) is frequently associated with the Epstein-Barr virus (EBV) and manifests as non-mass-forming microscopic lesions within fibrin-rich lesions. Herein, we describe the cytological features of FA-DLBCL. CASE REPORT: A 72-year-old man presented with a large retroperitoneal cystic mass that was treated by cyst aspiration and laparoscopic excision. Individually dispersed large, atypical cells in a necrotic background contained scant cytoplasm and hyperchromatic nuclei with irregular nuclear contours, frequent karyorrhectic debris, and mitotic figures. A fibrinous exudate with necrotic material attached to the inner surface of the cystic mass contained large, atypical cells that were individually scattered or arranged in small clusters. These were positive for cluster of differentiation 20 and Epstein-Barr virus-encoded RNA in situ hybridization. CONCLUSION: We cytologically characterized FA-DLBCL as large, atypical cells that were individually scattered or arranged in small clusters in a necrotic background. To the best of our knowledge, we revealed the cytological features of FA-DLBCL.


Cysts , Fibrin , Lymphoma, Large B-Cell, Diffuse , Humans , Male , Aged , Lymphoma, Large B-Cell, Diffuse/pathology , Fibrin/metabolism , Cysts/pathology , Herpesvirus 4, Human/genetics , Herpesvirus 4, Human/isolation & purification , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/pathology , Retroperitoneal Neoplasms/pathology , Tomography, X-Ray Computed
7.
Endokrynol Pol ; 75(2): 179-182, 2024.
Article En | MEDLINE | ID: mdl-38646990

INTRODUCTION: The objective was to investigate the correlation between Epstein-Barr virus (EBV) and human papillomavirus (HPV) infection in the development of benign thyroid lesions. MATERIAL AND METHODS: 29 cases of Hashimoto's thyroiditis (HT), 133 cases of thyroid adenoma, and 34 cases of HT with thyroid adenoma paraffin embedded tissue samples were used for EBV and HPV quantitative detection. RESULTS: None of the tissue samples carried HPV DNA. In HT tissue samples, the positive rate of EBV was 55.2% (16/29). In thyroid adenoma tissue samples, the positive rate was 37.6% (50/133). In HT combined with thyroid adenoma tissue samples, the positive rate of EBV was 67.6% (23/34). There was no correlation between EBV infection and clinical features such as age and gender. CONCLUSION: The occurrence and development of benign thyroid lesions are closely related to EBV infection. HT combined with thyroid adenoma may be more susceptible to EBV infection than simple HT and thyroid adenoma, which provides a new idea for the diagnosis and treatment of benign thyroid lesions.


Epstein-Barr Virus Infections , Hashimoto Disease , Herpesvirus 4, Human , Papillomavirus Infections , Thyroid Neoplasms , Humans , Female , Male , Epstein-Barr Virus Infections/complications , Adult , Middle Aged , Hashimoto Disease/virology , Herpesvirus 4, Human/isolation & purification , Thyroid Neoplasms/virology , Papillomavirus Infections/complications , Papillomavirus Infections/diagnosis , Adenoma/virology , Papillomaviridae/isolation & purification , DNA, Viral/analysis , Aged , Human Papillomavirus Viruses
8.
Arch Iran Med ; 27(4): 191-199, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38685845

BACKGROUND: Gastric cancer is the fourth leading cause of cancer-related deaths in the world. The identification of gastric cancer subtypes related to recognizable microbial agents may play a pivotal role in the targeted prevention and treatment of this cancer. The current study is conducted to define the frequency of Epstein-Barr virus (EBV) infection in gastric cancers of four major provinces, with different incidence rates of gastric cancers, in Iran. METHODS: Paraffin blocks of 682 cases of various types of gastric cancer from Tehran, South and North areas of Iran were collected. Twelve tissue microarray (TMA) blocks were constructed from these blocks. Localization of EBV in tumors was assessed by in situ hybridization (ISH) for EBV-encoded RNA (EBER). Chi-squared test was used to evaluate the statistical significance between EBV-associated gastric cancer (EBVaGC) and clinicopathologic tumor characteristics. RESULTS: Fourteen out of 682 cases (2.1%) of gastric adenocarcinoma were EBER-positive. EBER was positive in 8 out of 22 (36.4%) of medullary carcinomas and 6 out of 660 (0.9%) of non-medullary type, which was a statistically significant difference (P<0.001). The EBVaGCs were more frequent in younger age (P=0.009) and also showed a trend toward the lower stage of the tumor (P=0.075). CONCLUSION: EBV-associated gastric adenocarcinoma has a low prevalence in Iran. This finding can be due to epidemiologic differences in risk factors and exposures, and the low number of gastric medullary carcinomas in the population. It may also be related to gastric tumor heterogeneity not detected with the TMA technique.


Adenocarcinoma , Epstein-Barr Virus Infections , Herpesvirus 4, Human , In Situ Hybridization , Stomach Neoplasms , Tissue Array Analysis , Humans , Stomach Neoplasms/virology , Stomach Neoplasms/epidemiology , Iran/epidemiology , Male , Female , Middle Aged , Epstein-Barr Virus Infections/epidemiology , Epstein-Barr Virus Infections/complications , Herpesvirus 4, Human/genetics , Herpesvirus 4, Human/isolation & purification , Aged , Adenocarcinoma/virology , Adenocarcinoma/epidemiology , Adult , RNA, Viral/analysis , Aged, 80 and over
9.
Viral Immunol ; 37(4): 177-185, 2024 05.
Article En | MEDLINE | ID: mdl-38625025

Viral infections are major causes of mortality in solid-organ and hematopoietic stem cell transplant recipients. Epstein-Barr virus (EBV) and Parvovirus B19 (B19V) are among the common viral infections after transplantation and were recommended for increased screening in relevant guidelines. Therefore, the development of rapid, specific, and cost-effective diagnostic methods for EBV and B19V is of paramount importance. We applied Fluorescence of Loop Primer Upon Self-Dequenching Loop-mediated Isothermal Amplification (FLOS-LAMP) for the first time to develop a novel multiplex assay for the detection of EBV and B19V; the fluorophore attached to the probe are self-quenched in unbound state. After binding to the dumbbell-shaped DNA target, the fluorophore is dequenched, resulting in fluorescence development. The novel multiplex FLOS-LAMP assay was optimized by testing various ratios of primer sets. This novel assay, with great specificity, did not cross-react with the common virus. For the detection of EBV and B19V, the limits of detection could reach 969 and 798 copies/µL, respectively, and the assay could be completed within 25 min. Applying this novel assay to detect 200 clinical transplant individuals indicated that the novel assay had high specificity and good sensitivity. We developed multiplex FLOS-LAMP assay for the detection of EBV and B19V, which has the potential to become an important tool for clinical transplant patient screening.


Epstein-Barr Virus Infections , Herpesvirus 4, Human , Molecular Diagnostic Techniques , Nucleic Acid Amplification Techniques , Parvovirus B19, Human , Sensitivity and Specificity , Humans , Herpesvirus 4, Human/genetics , Herpesvirus 4, Human/isolation & purification , Nucleic Acid Amplification Techniques/methods , Parvovirus B19, Human/genetics , Parvovirus B19, Human/isolation & purification , Epstein-Barr Virus Infections/diagnosis , Epstein-Barr Virus Infections/virology , Molecular Diagnostic Techniques/methods , Fluorescence , DNA Primers/genetics , Transplant Recipients , Parvoviridae Infections/diagnosis , Parvoviridae Infections/virology , DNA, Viral/genetics , Organ Transplantation
10.
Ann Diagn Pathol ; 70: 152286, 2024 Jun.
Article En | MEDLINE | ID: mdl-38447253

Epstein-Barr virus (EBV) is responsible for many B cell lymphoproliferative disorders (LPD) spanning subclinical infection to immunodeficiency-related neoplasms. EBV establishes a latent infection in the host B cell as defined histologically by the expression of EBV latent membrane proteins and nuclear antigens. Herein, we characterize the latency patterns of immunodeficiency-related neoplasms including post-transplant lymphoproliferative disorders (PTLD) and therapy-related LPD (formerly iatrogenic) with latent membrane protein-1 (LMP-1) and EBV nuclear antigen-2 (EBNA-2) immunohistochemistry. The latency pattern was correlated with immunodeficiency and dysregulation (IDD) status and time from transplant procedure. 38 cases of EBV+ PTLD in comparison to 27 cases of classic Hodgkin lymphoma (CHL) and diffuse large B cell lymphoma (DLBCL) arising in either the therapy-related immunodeficiency setting (n = 12) or without an identified immunodeficiency (n = 15) were evaluated for EBV-encoded small RNAs by in situ hybridization (EBER-ISH) and for LMP-1 and EBNA-2 by immunohistochemistry. A full spectrum of EBV latency patterns was observed across PTLD in contrast to CHL and DLBCL arising in the therapy-related immunodeficiency setting. Polymorphic-PTLD (12 of 16 cases, 75 %) and DLBCL-PTLD (9 of 11 cases, 82 %) showed the greatest proportion of cases with latency III pattern. Whereas, EBV+ CHL in an immunocompetent patient showed exclusively latency II pattern (13 of 13 cases, 100 %). The majority of EBV+ PTLD occurred by three years of transplant procedure date and were enriched for latency III pattern (21 of 22 cases, 95 %). Immunohistochemical identification of EBV latency by LMP-1 and EBNA-2 can help classify PTLD in comparison to other EBV+ B cell LPD and lymphomas arising in therapy-related immunodeficiency and non-immunodeficiency settings.


Epstein-Barr Virus Infections , Epstein-Barr Virus Nuclear Antigens , Herpesvirus 4, Human , Hodgkin Disease , Lymphoma, Large B-Cell, Diffuse , Lymphoproliferative Disorders , Viral Matrix Proteins , Viral Proteins , Virus Latency , Humans , Lymphoproliferative Disorders/virology , Lymphoproliferative Disorders/pathology , Lymphoproliferative Disorders/diagnosis , Herpesvirus 4, Human/isolation & purification , Epstein-Barr Virus Infections/virology , Epstein-Barr Virus Infections/complications , Male , Epstein-Barr Virus Nuclear Antigens/metabolism , Female , Adult , Middle Aged , Viral Matrix Proteins/metabolism , Hodgkin Disease/virology , Hodgkin Disease/pathology , Lymphoma, Large B-Cell, Diffuse/virology , Lymphoma, Large B-Cell, Diffuse/pathology , Aged , Young Adult , Adolescent , Immunohistochemistry , Child , Lymphoma/virology , Lymphoma/pathology , In Situ Hybridization
12.
J Natl Cancer Inst ; 116(5): 665-672, 2024 May 08.
Article En | MEDLINE | ID: mdl-38171488

BACKGROUND: Although contrast-enhanced magnetic resonance imaging (MRI) detects early-stage nasopharyngeal carcinoma (NPC) not detected by endoscopic-guided biopsy (EGB), a short contrast-free screening MRI would be desirable for NPC screening programs. This study evaluated a screening MRI in a plasma Epstein-Barr virus (EBV)-DNA NPC screening program. METHODS: EBV-DNA-screen-positive patients underwent endoscopy, and endoscopy-positive patients underwent EGB. EGB was negative if the biopsy was negative or was not performed. Patients also underwent a screening MRI. Diagnostic performance was based on histologic confirmation of NPC in the initial study or during a follow-up period of at least 2 years. RESULTS: The study prospectively recruited 354 patients for MRI and endoscopy; 40/354 (11.3%) endoscopy-positive patients underwent EGB. Eighteen had NPC (5.1%), and 336 without NPC (94.9%) were followed up for a median of 44.8 months. MRI detected additional NPCs in 3/18 (16.7%) endoscopy-negative and 2/18 (11.1%) EGB-negative patients (stage I/II, n = 4; stage III, n = 1). None of the 24 EGB-negative patients who were MRI-negative had NPC. MRI missed NPC in 2/18 (11.1%), one of which was also endoscopy-negative. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI, endoscopy, and EGB were 88.9%, 91.1%, 34.8%, 99.4%, and 91.0%; 77.8%, 92.3%, 35.0%, 98.7%, and 91.5%; and 66.7%, 92.3%, 31.6%, 98.1%, and 91.0%, respectively. CONCLUSION: A quick contrast-free screening MRI complements endoscopy in NPC screening programs. In EBV-screen-positive patients, MRI enables early detection of NPC that is endoscopically occult or negative on EGB and increases confidence that NPC has not been missed.


Early Detection of Cancer , Epstein-Barr Virus Infections , Herpesvirus 4, Human , Magnetic Resonance Imaging , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Neoplasms/virology , Nasopharyngeal Neoplasms/diagnostic imaging , Nasopharyngeal Neoplasms/diagnosis , Nasopharyngeal Neoplasms/pathology , Male , Middle Aged , Female , Magnetic Resonance Imaging/methods , Early Detection of Cancer/methods , Adult , Herpesvirus 4, Human/isolation & purification , Nasopharyngeal Carcinoma/virology , Nasopharyngeal Carcinoma/diagnostic imaging , Nasopharyngeal Carcinoma/diagnosis , Nasopharyngeal Carcinoma/pathology , Prospective Studies , Aged , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/diagnosis , DNA, Viral/blood , Carcinoma/diagnostic imaging , Carcinoma/virology , Carcinoma/diagnosis , Carcinoma/pathology , Sensitivity and Specificity , Endoscopy/methods , Neoplasm Staging , Mass Screening/methods , Contrast Media/administration & dosage
13.
Nature ; 617(7961): 574-580, 2023 May.
Article En | MEDLINE | ID: mdl-36996871

As of August 2022, clusters of acute severe hepatitis of unknown aetiology in children have been reported from 35 countries, including the USA1,2. Previous studies have found human adenoviruses (HAdVs) in the blood from patients in Europe and the USA3-7, although it is unclear whether this virus is causative. Here we used PCR testing, viral enrichment-based sequencing and agnostic metagenomic sequencing to analyse samples from 16 HAdV-positive cases from 1 October 2021 to 22 May 2022, in parallel with 113 controls. In blood from 14 cases, adeno-associated virus type 2 (AAV2) sequences were detected in 93% (13 of 14), compared to 4 (3.5%) of 113 controls (P < 0.001) and to 0 of 30 patients with hepatitis of defined aetiology (P < 0.001). In controls, HAdV type 41 was detected in blood from 9 (39.1%) of the 23 patients with acute gastroenteritis (without hepatitis), including 8 of 9 patients with positive stool HAdV testing, but co-infection with AAV2 was observed in only 3 (13.0%) of these 23 patients versus 93% of cases (P < 0.001). Co-infections by Epstein-Barr virus, human herpesvirus 6 and/or enterovirus A71 were also detected in 12 (85.7%) of 14 cases, with higher herpesvirus detection in cases versus controls (P < 0.001). Our findings suggest that the severity of the disease is related to co-infections involving AAV2 and one or more helper viruses.


Adenovirus Infections, Human , Coinfection , Dependovirus , Hepatitis , Child , Humans , Acute Disease , Adenovirus Infections, Human/epidemiology , Adenovirus Infections, Human/virology , Coinfection/epidemiology , Coinfection/virology , Dependovirus/genetics , Dependovirus/isolation & purification , Epstein-Barr Virus Infections/epidemiology , Epstein-Barr Virus Infections/virology , Hepatitis/epidemiology , Hepatitis/virology , Herpesvirus 4, Human/isolation & purification , Herpesvirus 6, Human/isolation & purification , Enterovirus A, Human/isolation & purification , Helper Viruses/isolation & purification
14.
Stomatologiia (Mosk) ; 101(3): 18-21, 2022.
Article Ru | MEDLINE | ID: mdl-35640174

THE AIM OF THE STUDY: The study by the method of tissue polymerase chain reaction of the species composition of the microbiota of lesions of the oral mucosa in patients with bullous lesions. MATERIAL AND METHODS: Biopsy specimens of the oral mucosa of 51 patients were studied by the polymerase chain reaction method, of which 14 patients with pemphigus vulgaris, 17 patients with pemphigoid bullosa, and 20 patients with the bullous form of ruber lichen planus. 4 types of microorganisms have been identified - Fusobacterium, Streptococcus pneumoniae, Candida albicans, Ureaplasma spp. and viruses - Human Papillomavirus 16, Epstein-Barr virus and Citomegalovirus. RESULTS: In the study of the microbiota of bullous lesions, associations of microorganisms and viruses were established in a significant number of cases. Associations of Str.pneumoniae and C. albicans were quite common in patients with pemphigus vulgaris in 26.3%, pemphigoid bullosa in 20.0%, and in patients with the bullous form of ruber lichen planus in 14.3% of cases. In patients with pemphigus vulgaris, the association of Str.pneumoniae, C. albicans and EBV was noted in 31.6% of cases. In patients with the bullous form of ruber lichen planus in a high percentage of cases (28.6%), the associations of Str. pneumoniae, EBV and CMV. CONCLUSION: Identification at earlier stages of management of patients with bullous lesions Str. pneumoniae, Candida albicans, and Fusobacterium associated with herpes viruses should be regarded as one of the triggering mechanisms of an autoimmune conflict, which subsequently causes a specific clinical picture of these diseases.


Microbiota , Mouth Mucosa/pathology , Blister/microbiology , Blister/virology , Candida albicans/isolation & purification , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/pathology , Fusobacterium/isolation & purification , Herpesvirus 4, Human/isolation & purification , Humans , Lichen Planus/complications , Lichen Planus/pathology , Mouth Mucosa/microbiology , Mouth Mucosa/virology , Pemphigoid, Bullous/pathology , Pemphigus/complications , Pemphigus/pathology , Streptococcus pneumoniae/isolation & purification
16.
Medicine (Baltimore) ; 101(9): e28806, 2022 Mar 04.
Article En | MEDLINE | ID: mdl-35244038

RATIONALE: Epstein-Barr virus-associated smooth muscle tumors (EBV-SMT) are rare, virally-induced malignancies that occur almost exclusively in immunocompromised individuals. We report a very rare case of a dura-based EBV-SMT with superimposed local cryptococcal infection. PATIENT CONCERNS: An adult male with a history of untreated acquired immunodeficiency syndrome presented to our hospital with worsening headaches, diarrhea, and diffuse myalgias. DIAGNOSES: Blood cultures were positive for methicillin-resistant Staphylococcus aureus and Cryptococcus neoformans serum antigen. Magnetic resonance imaging revealed 2 adjacent enhancing masses in the right temporal lobe, perilesional edema, and mass effect of the right lateral ventricle. Histological examination and immunohistochemical stains of the surgical specimen were consistent with EBV-SMT. Cryptococcus organisms were identified within the neoplasm. INTERVENTIONS: The patient underwent complete tumor resection, received an extended course of amphotericin and flucytosine, and was restarted on antiretroviral therapy. OUTCOMES: The patient was discharged from the hospital with no focal neurological deficits. LESSONS: Epstein-Barr virus associated smooth muscle tumors are rare malignancies that occur in immunocompromised patients. Prognosis is largely dependent on immune reconstitution and treatment of concomitant infections.


Cryptococcus neoformans/isolation & purification , Epstein-Barr Virus Infections/pathology , Herpesvirus 4, Human/isolation & purification , Magnetic Resonance Imaging/methods , Smooth Muscle Tumor/pathology , Superinfection , Temporal Lobe/diagnostic imaging , Adult , Amphotericin B/therapeutic use , Antiretroviral Therapy, Highly Active , Epstein-Barr Virus Infections/complications , Flucytosine/therapeutic use , HIV Infections/drug therapy , Herpesvirus 4, Human/genetics , Humans , Immunocompromised Host , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Opportunistic Infections , Smooth Muscle Tumor/virology
18.
Br J Surg ; 109(3): 291-297, 2022 02 24.
Article En | MEDLINE | ID: mdl-35179206

BACKGROUND: Patients with Epstein-Barr virus-positive gastric cancers or those with microsatellite instability appear to have a favourable prognosis. However, the prognostic value of the chromosomal status (chromosome-stable (CS) versus chromosomal instable (CIN)) remains unclear in gastric cancer. METHODS: Gene copy number aberrations (CNAs) were determined in 16 CIN-associated genes in a retrospective study including test and validation cohorts of patients with gastric cancer. Patients were stratified into CS (no CNA), CINlow (1-2 CNAs) or CINhigh (3 or more CNAs). The relationship between chromosomal status, clinicopathological variables, and overall survival (OS) was analysed. The relationship between chromosomal status, p53 expression, and tumour infiltrating immune cells was also assessed and validated externally. RESULTS: The test and validation cohorts included 206 and 748 patients, respectively. CINlow and CINhigh were seen in 35.0 and 15.0 per cent of patients, respectively, in the test cohort, and 48.5 and 20.7 per cent in the validation cohort. Patients with CINhigh gastric cancer had the poorest OS in the test and validation cohorts. In multivariable analysis, CINlow, CINhigh and pTNM stage III-IV (P < 0.001) were independently associated with poor OS. CIN was associated with high p53 expression and low immune cell infiltration. CONCLUSION: CIN may be a potential new prognostic biomarker independent of pTNM stage in gastric cancer. Patients with gastric cancer demonstrating CIN appear to be immunosuppressed, which might represent one of the underlying mechanisms explaining the poor survival and may help guide future therapeutic decisions.


Adenocarcinoma/genetics , Adenocarcinoma/immunology , Chromosomal Instability , Gene Dosage , Immunocompromised Host , Stomach Neoplasms/genetics , Stomach Neoplasms/immunology , Adenocarcinoma/pathology , Adenocarcinoma/virology , Aged , Biomarkers, Tumor/genetics , Female , Genes, p53/genetics , Herpesvirus 4, Human/isolation & purification , Humans , Male , Middle Aged , Mutation , Neoplasm Staging , Prognosis , Retrospective Studies , Stomach Neoplasms/pathology , Stomach Neoplasms/virology
19.
Int J Cancer ; 150(2): 327-334, 2022 01 15.
Article En | MEDLINE | ID: mdl-34520566

Elevated Epstein-Barr virus (EBV) DNA load is common in lymphomas. However, it remains unclear whether the disparity in viral load and its prognostic value in lymphomas are correlated with Epstein-Barr encoding region (EBER) status. In this retrospective multicenter study, we collected the data of pretreatment whole blood EBV DNA (pre-EBV DNA) and EBER status and evaluated their disparity and prognostic values in lymphomas. A total of 454 lymphoma patients from December 2014 to August 2020 were retrospectively retrieved. Mann-Whitney U test, Kruskal-Wallis test and Bonferroni's adjustment were used to explore the disparity of EBV DNA and EBER status in lymphomas. Time-dependent receiver operating characteristic analysis and MaxStat analysis were used to determine optimal cutoff points of pre-EBV DNA load. Univariable and multivariable Cox proportional hazards models were established for the estimation of prognostic factors. The positive rate of EBV DNA in natural killer T-cell lymphoma (NKTL) patients was higher than that in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Hodgkin lymphoma (HL) patients, and the median positive pre-EBV copy number of NKTL was also higher than that of FL and DLBCL. EBV DNA could clearly distinguish the prognosis of DLBCL, NKTL, HL and peripheral T-cell lymphoma, and the integration of EBER status and EBV DNA could differentiate the prognosis of HL patients. Multivariable results revealed that pre-EBV DNA load had an effect on the prognosis of NKTL, FL and DLBCL. The status of pre-EBV DNA and EBER were disparate. Whole blood pre-EBV DNA predicted the prognosis of lymphomas, and the combination of EBV and EBER status could differentiate the prognosis of HL.


DNA, Viral/genetics , Epstein-Barr Virus Infections/complications , Herpesvirus 4, Human/genetics , Hodgkin Disease/diagnosis , Lymphoma, Follicular/diagnosis , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, T-Cell/diagnosis , Adult , Aged , Aged, 80 and over , DNA, Viral/analysis , Diagnosis, Differential , Epstein-Barr Virus Infections/virology , Female , Follow-Up Studies , Herpesvirus 4, Human/isolation & purification , Hodgkin Disease/epidemiology , Hodgkin Disease/virology , Humans , Lymphoma, Follicular/epidemiology , Lymphoma, Follicular/virology , Lymphoma, Large B-Cell, Diffuse/epidemiology , Lymphoma, Large B-Cell, Diffuse/virology , Lymphoma, T-Cell/epidemiology , Lymphoma, T-Cell/virology , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate
20.
Int J Cancer ; 150(5): 753-760, 2022 03 01.
Article En | MEDLINE | ID: mdl-34626122

Few data exist on Epstein-Barr virus (EBV) prevalence across the full spectrum of lymphoma subtypes, particularly in sub-Saharan Africa. The objective of our study was to test the presence of EBV in a nationally representative sample of malignant lymphomas diagnosed in the Butaro Cancer Center of Excellence (BCCOE) in Rwanda. Of 102 Hodgkin (HL) and 378 non-Hodgkin lymphomas (NHL) diagnosed in BCCOE between 2012 and 2018, 52 HL and 207 NHL were successfully tested by EBV-encoding RNA in situ hybridization. EBV prevalence was 54% in HL, being detected in all classical HL subtypes: mixed-cellularity (n = 3/8), nodular-sclerosis (n = 7/17) and lymphocyte-rich (n = 2/3). EBV prevalence was 9% in NHL, being 10% among 158 B-cell NHL, 3% among 35 T-cell NHL and the single NK-cell NHL was EBV-positive. Among B-cell NHL, EBV was present in the majority of Burkitt (n = 8/13), and was also rarely detected in follicular (n = 1/4) and acute B-cell lymphoblastic (n = 1/45) lymphomas. Five of the 45 (11%) diffuse large B-cell lymphomas (DLBCLs) were EBV-positive, including three out of five plasmablastic lymphoma (PBL). Of 39 HL and 163 NHL of known human immunodeficiency virus (HIV) status, 2 (5%) and 14 (9%) were HIV-positive, respectively, of which only four were also EBV-positive (2 PBL, 2 HL). In summary, we report rare regional-level data on the association of EBV with classical HL, Burkitt and DLBCLs, and report sporadic detection in other subtypes possibly related to EBV. Such data inform the burden of disease caused by EBV and can help guide application of future advances in EBV-specific prevention and therapeutics.


Herpesvirus 4, Human/isolation & purification , Lymphoma/virology , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Lymphoma/classification , Lymphoma/etiology , Male , Middle Aged , RNA, Viral/analysis , Rwanda , Time Factors , Young Adult
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